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Open Access 01-12-2018 | Research

Isolated nigral degeneration without pathological protein aggregation in autopsied brains with LRRK2 p.R1441H homozygous and heterozygous mutations

Authors: Masashi Takanashi, Manabu Funayama, Eiji Matsuura, Hiroyo Yoshino, Yuanzhe Li, Sho Tsuyama, Hiroshi Takashima, Kenya Nishioka, Nobutaka Hattori

Published in: Acta Neuropathologica Communications | Issue 1/2018

Abstract

Leucine-rich repeat kinase 2 (LRRK2) is the most common causative gene for autosomal dominant Parkinson’s disease (PD) and is also known to be a susceptibility gene for sporadic PD. Although clinical symptoms with LRRK2 mutations are similar to those in sporadic PD, their pathologies are heterogeneous and include nigral degeneration with abnormal inclusions containing alpha-synuclein, tau, TAR DNA-binding protein 43, and ubiquitin, or pure nigral degeneration with no protein aggregation pathologies. We discovered two families harboring heterozygous and homozygous c.4332 G > A; p.R1441H in LRRK2 with consanguinity, sharing a common founder. They lived in the city of Makurazaki, located in a rural area of the southern region, the Kagoshima prefecture, in Kyushu, Japan. All patients presented late-onset parkinsonism without apparent cognitive decline and demonstrated a good response to levodopa. We obtained three autopsied cases that all presented with isolated nigral degeneration with no alpha-synuclein or other protein inclusions. This is the first report of neuropathological findings in patients with LRRK2 p.R1441H mutations that includes both homozygous and heterozygous mutations. Our findings in this study suggest that isolated nigral degeneration is the primary pathology in patients with LRRK2 p.R1441H mutations, and that protein aggregation of alpha-synuclein or tau might be secondary changes.

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Title: Isolated nigral degeneration without pathological protein aggregation in autopsied brains with LRRK2 p.R1441H homozygous and heterozygous mutations
Authors: Masashi Takanashi
Manabu Funayama
Eiji Matsuura
Hiroyo Yoshino
Yuanzhe Li
Sho Tsuyama
Hiroshi Takashima
Kenya Nishioka
Nobutaka Hattori
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2018
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-018-0617-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Isolated nigral degeneration without pathological protein aggregation in autopsied brains with LRRK2 p.R1441H homozygous and heterozygous mutations

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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